My confidence in two-day cardiopulmonary exercise testing (CPET) is pretty obvious on this blog. A new study from ME/CFS experts Dr. Chris Snell, Staci Stevens, Dr. Todd Davenport, and Dr. Mark VanNess supplies hard data that shows how important a two-day maximal CPET is for diagnosis and documenting ME/CFS. The Physical Therapy Journal has made the author manuscript available (behind a paywall), and so that version I review here is not necessarily the final version that will be published by the journal.
The purpose of this study was to establish whether the objective measurements in CPET could distinguish patients with CFS from healthy controls. The study enrolled 51 female CFS patients and 10 female sedentary controls. The CFS patients were diagnosed using the Fukuda criteria, and they also reported symptom exacerbation after activity. All subjects completed two maximal effort CPETs conducted 24 hours apart. Unfortunately, the study did not include testing for post-exercise gene expression (like the Light study). No evaluation or follow up is reported, so we do not know how long it took the subjects to recover from the testing.
In Test 1, the CFS patients did not perform as well as controls. Multiple measurements were lower in the CFS group, including VO2max, peak workload, and workload at the anaerobic threshold. However, only the peak workload difference was statistically significant. In Test 2, the differences were quite dramatic. The controls performed the same or even better on the second test. But the CFS patients demonstrated a drop in VO2max, oxygen consumption at the anaerobic threshold, peak workload, and workload at the anaerobic threshold. The mean for the last value – workload at the anaerobic threshold – dropped by more than 50%. Respiratory measurements prove that all subjects gave a maximal effort in both tests, so the reduction is not due to lack of effort.
So what does this mean? The inability of people with CFS to reproduce their CPET results on day two is extraordinary. The authors state that it “could be utilized diagnostically as an objective indicator of abnormal post-exertional response, and possibly even a biomarker for this condition.” In fact, statistical analysis of the results correctly classified CFS patients and controls with 95.1% accuracy.
Healthy individuals stay below the anaerobic threshold most of the time. But this study showed that for many CFS patients, even activities of daily living require them to push past their anaerobic thresholds. My own test results demonstrated the same impairment. This could explain not only our limitations on good days, but why those limitations shrink during post-exertional malaise.
This study demonstrates the importance of using a two-day test protocol. While there were differences between patients and controls on the first day, only the CFS patients demonstrated a dramatic drop in performance on the second day. This significant reduction in performance appears to be unique to CFS. A recent study in patients with sarcoidosis (an inflammatory condition) failed to find any difference in CPET results between patients and controls, despite using a two day protocol.
One of the questions this paper cannot answer is: why? What do these results tell us about the underlying cause? The authors say, “It is very possible that a synergy of small effects across multiple systems is responsible for the poor exercise performance of the individuals with CFS in this study.” The results are consistent with reduced oxygen carrying capacity, possibly due to low blood volume, cardiac abnormalities, or autonomic dysfunction.
The conclusion of the paper is worth quoting at length:
In conclusion, a serial CPET protocol with measurement of expired gases demonstrates efficacy in distinguishing between individuals with CFS and sedentary, but otherwise healthy controls. As in the only other studies identified employing a dual CPET paradigm with measurement of expired gases, individuals with CFS showed a decrease in performance on the second test that was not seen in controls. This functional deficit may provide an objective indication of PEM. Despite considerable patient heterogeneity with respect to illness duration and type of onset, analysis of data from the second test was able to correctly classify 49 out of 51 individuals with CFS and 9 out of 10 controls. Non-invasive biomarkers for CFS do not currently exist. Physical therapists may consider the use of CPET performance measures to differentiate between individuals with CFS and otherwise non-disabled sedentary persons. Work efficiency (i.e. oxygen consumption and work output) at the ventilatory/anaerobic threshold appears to have diagnostic potential for CFS. (emphasis added)
This paper had a long journey to publication. The manuscript was submitted in October 2011, but was not accepted until June 2013. I hope its publication will lead to wider use of the two day maximal CPET protocol, particularly in research like the CDC’s multisite study. The suffering and agony of a two day test can be severe, as my own experience shows. But an objective way to diagnose CFS has held this field back for thirty years. If the two day CPET can provide objective diagnosis, then I say let’s go full speed ahead.